Periodontal disease is the most common cause of tooth loss. The disease is caused by interaction of microorganisms with host defense mechanisms resulting in damage to the connective tissues and bone. Similar connective tissue alterations are an important component of many chronic diseases. The mechanisms underlying alterations of this type have not been elucidated. We propose to continue our analysis of normal and diseased connective tissue matrix components and to learn what role fibroblasts play in the pathologic alterations. We will study the quantity, location and distribution of alpha-I trimer collagen which is present in diseased gingiva and is made by cells from this tissue maintained in vitro. This collagen will be purified and characterized with regard to digestability with collagenase and other enzymes, ability to undergo crosslinking with lysyl oxidase and capacity to form fibrils. In addition a group of noncollagenous proteins found in normal dog gingiva but not in diseased dog gingiva will be extracted and purified. The relationship between fibroblast function and pathologic alteration will be investigated as follows. We propose that fibroblast activities are regulated at least in part by the interaction of cell surface binding sites with ligands present in the extracellular environment. We will assess the importance of two such ligands which are already known to affect fibroblast functions. These are prostaglandin and the C1 component of complement. The presence, density and affinity of cell-surface binding sites for prostaglandin will be determined. Cell movement will be measured by cinematography, cell growth by DNA labeling and cell counting, and synthetic activity by radiolabeling and chromatographic techniques. Successful completion of the project will reveal how fibroblasts participate in the pathologic alterations in numerous diseases and may lead to new or improved methods of intervention or prevention.